This invention relates to a novel soluble form of rapamycin 42-ester with 3-hydroxy-2-(hydroxymethyl)-2-methylpropionic acid.
Crystalline rapamycin 42-ester with 3-hydroxy-2-(hydroxymethyl)-2-methylpropionic acid (CCI-779) has poor solubility, which leads to slow dissolution of the solid crystalline form, typically oral solid dosage forms including tablets, in physiologically acceptable solvents.
The dissolution and absorption of rapamycin 42-ester with 3-hydroxy-2-(hydroxymethyl)-2-methylpropionic acid has reportedly been improved by the formation of solid dispersions with carrier systems using co-precipitate technique, spray drying, use of nanoparticles, and wet granulation methods. However, while the art asserts that rapamycin can be in crystalline or amorphous form, amorphous rapamycin 42-ester with 3-hydroxy-2-(hydroxymethyl)-2-methylpropionic acid has never been previously prepared, isolated and/or characterized.
Since rapamycin 42-ester with 3-hydroxy-2-(hydroxymethyl)-2-methylpropionic acid is a therapeutically active compound, it is highly desirable to obtain amorphous rapamycin 42-ester with 3-hydroxy-2-(hydroxymethyl)-2-methylpropionic acid that has improved solubility, dissolution rate and bioavailability.